CN109310718B - Flora improving agent in upper digestive tract - Google Patents
Flora improving agent in upper digestive tract Download PDFInfo
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- CN109310718B CN109310718B CN201780038418.3A CN201780038418A CN109310718B CN 109310718 B CN109310718 B CN 109310718B CN 201780038418 A CN201780038418 A CN 201780038418A CN 109310718 B CN109310718 B CN 109310718B
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- upper gastrointestinal
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- lactic acid
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K2035/11—Medicinal preparations comprising living procariotic cells
- A61K2035/115—Probiotics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The problem is solved by an agent for improving the flora in the upper gastrointestinal tract, which is used for positive and negative helicobacter pylori and contains lactic acid bacteria as an active ingredient. The lactic acid bacteria are preferably lactic acid bacteria of the genus Lactobacillus, more preferably Lactobacillus gasseri (L.) (Lactobacillus gasseri) OLL2716 (FERM BP-6999). The improved upper gastrointestinal flora may be, for example, a reduction in upper gastrointestinal bifidobacteria and/or an increase in upper gastrointestinal prevotella.
Description
Technical Field
The present invention relates to an agent for improving upper gastrointestinal flora, and the like. Specifically, it relates to an agent for reducing upper gastrointestinal bifidobacterium that reduces upper gastrointestinal bifidobacterium and/or an agent for increasing upper gastrointestinal prevotella that increases upper gastrointestinal prevotella.
Background
In spite of the progress of endoscopic diagnosis, many cases have been seen in which symptoms cannot be explained in complaints of upper digestive system symptoms such as epigastric pain, discomfort, postprandial gastrointestional eating sensation, epigastric fullness, nausea/vomiting, epigastric pain (epigastric pain), and heartburn. Although there is a complaint of such digestive system symptoms, it is seen that organic diseases cannot be found by a general examination including an endoscope and clear symptoms cannot be obtained, and such a condition is called FD (functional dyspepsia), upper abdominal complaint (irregular upper abdominal symptoms), postprandial complaint (postprandial complaint), epigastric pain, or functional gastrointestinal disease).
Since these symptoms do not occur in organic diseases, there are cases where the symptoms are overlooked or misdiagnosed. Therefore, the quality of life (QOL) of a person with functional digestive tract disorders who is not diagnosed with a clear disease name is reduced despite such discomfort.
As a method for improving these symptoms, administration of serotonin or nitric oxide to release is known. However, since the administration described above involves side effects, prevention or improvement of functional digestive tract disorders by a method not involving side effects is desired.
Various proposals have been made so far for the prevention or amelioration of functional digestive tract disorders by a method not accompanied by side effects.
For example, patent documents 1 and 2 describe: functional digestive tract disorders are ameliorated by administration of glutamic acid, 5' -nucleotide, and the like (each claim 1).
Patent document 3 describes a functional gastrointestinal disorder preventing/ameliorating agent containing glutamic acid, arginine, and the like as active ingredients. The agent can be easily produced, has low cost and high safety, and is especially effective in treating upper gastrointestinal disorder (FD) such as abdominal pain, dyspepsia, and heartburn (pyrosis), and gastroesophageal reflux disease (GERD) (abstract).
As a technique for preventing or ameliorating functional digestive tract disorders using lactic acid bacteria, patent document 4 discloses bifidobacterium bifidum (hereinafter, sometimes referred to as "bifidobacterium") which is a bifidobacterium bifidumMycobacterium has helicobacter pylori: (Helicobacter pylori) (hereinafter, it may be referred to as helicobacter pylori. ) Has high viability even under aerobic conditions as in fermented milk drinks, and shows: ingestion of fermented milk drink containing the bifidobacterium improves the variably worried stomach syndrome (paragraphs 0011 and 0096).
Patent document 5 shows that: the strain Lactobacillus gasseri MCC1183 has a bactericidal activity against helicobacter pylori, and there are descriptions on anti-inflammatory agents and anti-ulcer agents for preventing or treating gastritis and foods and drinks (foods and drinks) suitable for indigestion, to which the findings are applied (paragraphs 0023 and 0052).
Patent document 6 describes: drugs for gastrointestinal enhancement (potentiating) containing lactobacillus (lactobacillus acidophilus, etc.), streptococcus (streptococcus) such as streptococcus faecalis, etc., and aloe vera (claims 1, 2, paragraph 0012) are described that gastric indigestion and abdominal fullness are also improved in gastrointestinal enhancement (paragraph 0043).
That is, a technique for improving functional digestive tract disorders by removing helicobacter pylori using a fermented milk beverage containing lactic acid bacteria such as bifidobacterium has been known. In addition, the use of Lactobacillus gasseri MCC1183 strain to remove helicobacter pylori has also been proposed to improve gastric indigestion. Further, it has been proposed to improve the feeling of stomach retention or abdominal fullness by using a drug for promoting gastrointestinal function containing lactic acid bacteria belonging to the genus Lactobacillus, lactic acid bacteria belonging to the genus Streptococcus, and aloe.
Documents of the prior art
Patent document
Patent document 1: international publication No. 2006/030980;
patent document 2: japanese patent No. 5067145;
patent document 3: international publication No. 2009/113594;
patent document 4: japanese patent No. 4881304;
patent document 5: japanese patent No. 5300772;
patent document 6: japanese patent laid-open publication No. 2012 and 126700;
patent document 7: japanese patent No. 4509250;
patent document 8: international publication No. 2015/129281.
Disclosure of Invention
On the other hand, as described in patent document 7, the present applicant has a patent right for a drug for sterilization and/or infection prevention of helicobacter pylori, which contains as an active ingredient a lactic acid bacterium having a high ability to sterilize helicobacter pylori, i.e., lactobacillus gasseri OLL2716 strain. This document describes: the medicament is used as an anti-gastritis drug or an anti-ulcer drug (claims 1, 3).
As described in patent document 8, the present applicant has found that: the Lactobacillus gasseri OLL2716 strain is effective for the prevention and/or improvement of functional digestive tract disorders.
However, it is not clear whether or not the Lactobacillus gasseri OLL2716 strain is effective as a prophylactic and/or ameliorating agent for functional digestive tract disorders, and which mechanism is used.
Therefore, the present inventors have conducted intensive studies to find that: in the upper gastrointestinal tract of patients with functional gastrointestinal disorders, bifidobacteria which cannot be found in healthy persons are present in the stomach, and it was found that the strain Lactobacillus gasseri OLL2716 is effective in reducing the number of bifidobacteria in the upper gastrointestinal tract.
In addition, the present inventors have conducted intensive studies to find that: the number of bacteria of prevotella in the stomach of a patient with functional gastrointestinal disorder was small as compared with that in the upper gastrointestinal tract (stomach) of a healthy person, and it was found that the L.gasseri OLL2716 strain was effective for increasing the number of bacteria of prevotella in the upper gastrointestinal tract.
In addition, as a result of examining the effect of reducing upper gastrointestinal bifidobacterium and the effect of increasing upper gastrointestinal prevotella of the L.gasseri OLL2716 strain, it was surprisingly found that the effect was not related to the sterilization of helicobacter pylori mediated by the L.gasseri OLL2716 strain.
Moreover, it was found that the L.gasseri OLL2716 strain was also able to decrease Bifidobacterium in the upper gastrointestinal tract and increase prevotella in the upper gastrointestinal tract in H.pylori-negative patients.
That is, it is clear that: the L.gasseri OLL2716 strain exerts a reducing effect on Bifidobacterium in the upper gastrointestinal tract and an increasing effect on Prevotella coli not only in those positive but also in those negative.
It is common technical knowledge that bifidobacterium is generally present in the intestine but not in the upper gastrointestinal tract such as the stomach, and it is also common technical knowledge that bifidobacterium is not present in the stomach of a patient with functional gastrointestinal disorder not related to organic diseases, but this time, it is known to subvert the common knowledge. Further, although it is common technical knowledge that the number of bacteria of prevotella intragastralis, which is represented by the stomach, is not considered to decrease even if functional gastrointestinal disorders unrelated to organic diseases are caused, this time, a finding which subverts the common knowledge is obtained.
The present invention has been made in view of the above circumstances, and an object thereof is to: an agent for improving the flora in the upper gastrointestinal tract, specifically an agent for reducing bifidobacteria in the upper gastrointestinal tract, or an agent for increasing prevotella in the upper gastrointestinal tract, is provided for both of those positive and negative helicobacter pylori.
In order to achieve the above object, the agent for improving the flora in the upper gastrointestinal tract of the present invention is used for positive and negative helicobacter pylori bacteria, and comprises a lactic acid bacterium as an active ingredient.
In the present invention, lactic acid bacteria belonging to the genus Lactobacillus are preferably used as lactic acid bacteria, and more preferably Lactobacillus gasseri (II) isLactobacillus gasseri) OLL2716 (FERM BP-6999) is used as Lactobacillus lactobacillus.
The present invention is preferably formulated as an agent for improving the flora in the upper gastrointestinal tract of a helicobacter pylori-negative subject.
In the present invention, it is preferable that the daily dose of the number of the lactic acid bacteria in human is 2X 107～5×1010Each 1g of the above lactobacillus culture contains 107In the case of more than one lactic acid bacterium, the daily dose of the lactic acid bacterium culture to a human is preferably 5 to 1000 g.
The agent for improving upper gastrointestinal flora of the present invention has a quick-acting property, which means that the agent exerts an effect of improving upper gastrointestinal flora within 4 weeks after ingestion.
Examples of the improvement of the upper gastrointestinal flora include a decrease in upper gastrointestinal bifidobacteria and an increase in upper gastrointestinal prevotella.
More specifically, the improvement of the upper gastrointestinal flora includes, for example, a decrease in bifidobacteria in the stomach and an increase in prevotella in the stomach.
Further, the agent for improving the upper gastrointestinal flora of the present invention is preferably provided in the form of a functional food such as a food, drink, health food, health functional food, or tonic.
According to the present invention, an agent for improving the flora in the upper gastrointestinal tract can be provided for both positive and negative helicobacter pylori cells.
Detailed Description
Hereinafter, preferred embodiments of the present invention will be described in detail.
An agent for improving upper gastrointestinal flora according to an embodiment of the present invention is characterized in that: is used for positive and negative helicobacter pylori, and contains lactobacillus as effective component.
According to the embodiment of the present invention, it is possible to provide an agent for improving the upper gastrointestinal flora, which comprises a lactic acid bacterium having a usual eating habit and having almost no side effects as an active ingredient. For example, according to the embodiment of the present invention, even in the case of a helicobacter pylori-negative person, an agent for improving the flora in the upper gastrointestinal tract can be provided.
Lactic acid bacteria are generally used in fermented foods such as yogurt, cheese, butter, and kimchi, and some lactic acid bacteria have a familiar flavor and are easily ingested.
The lactic acid bacterium in the embodiment of the present invention may be any lactic acid bacterium as long as it is a lactic acid bacterium that generates lactic acid by assimilating a saccharide, and may be of any genus, species, source, or the like. Among them, lactic acid bacteria of the genus Lactobacillus, particularly Lactobacillus gasseri (L.) (Lactobacillus gasseri) Lactobacillus gasseri OLL2716 (FERM BP-6999) can be suitably used.
The upper gastrointestinal flora in the embodiment of the present invention refers to bacteria in the upper gastrointestinal tract other than helicobacter pylori. In an embodiment of the present invention, it was found that: by taking Lactobacillus gasseri OLL2716 (FERM BP-6999), Bifidobacterium in the upper gastrointestinal tract is reduced and/or Prevotella in the upper gastrointestinal tract is increased, thereby approaching the upper gastrointestinal flora of healthy people. It is common technical knowledge that bifidobacterium is generally present in the intestine but not in the upper gastrointestinal tract represented by the stomach, and it is considered that bifidobacterium is not present in the stomach of a patient with functional gastrointestinal disorder not related to organic diseases, and this is also common technical knowledge, and this time, knowledge is obtained to subvert this common knowledge. Further, it is a common technical knowledge that the number of bacteria does not decrease even when a functional gastrointestinal disorder not related to an organic disease is caused in prevotella intragastralis typified by the stomach, and this time, a finding that subverts the common knowledge is obtained.
The functional gastrointestinal disorder in the embodiment of the present invention refers to a disease state in which an upper abdomen is uncertain about persistent complaints such as digestive ulcer and cancer symptoms, but digestive sensation, feeling of food retention in the stomach, feeling of fullness in the abdomen, nausea/vomiting, upper abdomen pain, loss of appetite, or abnormal defecation, etc., and refers to a symptom of a digestive system symptom with reproducibility in which a decrease in QOL of a patient is observed even if no organic disease of the digestive tract is observed. This functional digestive disorder refers to a disease hitherto diagnosed as chronic gastritis or gastritis, which is characterized by presenting symptoms of abdominal pain, stomach food retention, heartburn, and the like. Further, since such functional gastrointestinal disorders cannot be seen in organic diseases of the gastrointestinal tract, there are many theories such as abnormal transmission of the nervous system due to stress or the like, slight inflammation to such an extent that cannot be detected by an endoscope or the like, and a decrease in the motor function of the gastrointestinal tract, but these are not clear.
The digestive tract refers to a series of luminal organs involved in digestion from the mouth to the anus, and examples thereof include the pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), and large intestine. The upper digestive tract refers to pharynx, esophagus, stomach, and duodenum.
In addition, in the embodiment of the present invention, as an effective amount (intake amount) per day for humans, it is desirableThe number of bacteria to be ingested is preferably 2X 107～5×1010More preferably 5X 107～5×1010More preferably 1X 108～5×1010More preferably 5X 108～5×1010More preferably 5X 108～2×1010The mode is that the lactobacillus contains effective components in the flora improving agent in the upper gastrointestinal tract.
This is due to: if the number of bacteria to be ingested is less than 2X 107In the above mode, if lactic acid bacteria are contained in the agent for improving the flora in the upper gastrointestinal tract, it is difficult to obtain the effect of preventing and/or improving the functional gastrointestinal disorder in humans even if the number of ingested bacteria is more than 5X 1010The mode is that the flora improving agent in the upper gastrointestinal tract contains lactic acid bacteria, and the effect of the agent is not changed greatly.
In addition, in the embodiment of the present invention, as an effective amount (intake amount) per day for human, 10 is contained per 1g of the lactic acid bacterium culture7In the case of more than one lactic acid bacterium, it is preferable to include the lactic acid bacterium culture in the upper gastrointestinal flora improving agent so that the intake of the lactic acid bacterium is preferably 5 to 1000g, more preferably 10 to 1000g, further preferably 50 to 500g, further preferably 70 to 300g, further preferably 70 to 250g, and particularly preferably 80 to 200 g. Here, in the embodiment of the present invention, the effective amount (intake amount) of a human may be taken 1 time per day or may be taken twice or more.
The number of lactic acid bacteria contained in 1g of the lactic acid bacteria culture is 107More than one, and may be 107Or 1081, 109And so on. When the number of lactic acid bacteria contained in 1g of the lactic acid bacteria culture is increased, the number of lactic acid bacteria contained in an effective amount in the agent for improving upper gastrointestinal flora can be increased, the effective amount of the lactic acid bacteria culture can be reduced, and the same effect of improving upper gastrointestinal flora of a human can be obtained by taking a smaller amount of the lactic acid bacteria culture.
The lactic acid bacteria culture according to the embodiment of the present invention can be obtained by culturing (proliferating) lactic acid bacteria using a known medium component. Further, the number of lactic acid bacteria per unit weight of the culture solution can be increased by centrifuging the obtained lactic acid bacteria culture solution or the like. The lactic acid bacteria in the embodiment of the present invention may be in a state of being immediately cultured (proliferated), may be in a state of being mixed with a cryoprotectant or the like and frozen, or may be in a freeze-dried state. The lactic acid bacteria in the embodiment of the present invention may be live bacteria or dead bacteria, and preferably live bacteria.
In addition, commercially available products containing the lactic acid bacteria in the embodiments of the present invention may be used for convenience. For example, in the case of Lactobacillus gasseri: (Lactobacillus gasseri) For the purpose of convenience, OLL2716 (FERM BP-6999) "Mingzhi PROBIO YOGURT LG 21", which is sold by K.K., can be used. The commercially available product may be taken as it is or may be further processed. When the lactic acid bacterium and other ingestible components in the embodiment of the present invention are ingested together, the other ingestible components are not limited, and for example, milk components are suitably used. The milk component refers to a composition containing milk itself or a milk component obtained by processing milk, and includes all components containing milk components such as fresh milk (e.g., cow milk), reconstituted milk (e.g., milk powder, cream, butter), fermented milk (e.g., yogurt, cheese), milk products (e.g., whey, casein, lactose, whey minerals, and permeate), and the source and form of the components are not particularly limited.
Further, an agent for improving upper gastrointestinal flora according to an embodiment of the present invention is characterized in that: has quick action, and especially has effect in improving flora in upper digestive tract within 4 weeks. Needless to say, the intake of the agent for improving upper gastrointestinal flora according to the embodiment of the present invention is not limited to the continuous intake for longer than 4 weeks, but is preferably 4 weeks or longer, more preferably 8 weeks or longer, still more preferably 12 weeks or longer, still more preferably 16 weeks or longer, and still more preferably 20 weeks or longer.
The method of taking the agent for improving upper gastrointestinal flora according to the embodiment of the present invention and the frequency of taking the agent are not particularly limited. In the examples described later, the upper gastrointestinal flora improving agent was taken daily, and the preferred number of lactic acid bacteria per 1 day was shown in the above-described embodiments, but the upper gastrointestinal flora improving effect according to the embodiments of the present invention was not necessarily confirmed unless the agent was taken daily. The frequency of intake may be appropriately adjusted to, for example, 2 days 1 time, 3 days 1 time, 4 days 1 time, 5 days 1 time, 7 days (1 week) 1 time, 10 days 1 time, 1 month 1 time, or the like, as long as the effect is confirmed.
The agent for improving the upper gastrointestinal flora according to the embodiment of the present invention may be in the form of a single-dose package containing 1 meal, or may be in the form of a single-dose package containing the number of effective lactic acid bacteria.
For example, each of the single dose packages is preferably intended for ingestion of 2X 107～5×1010The form of the seed is contained, more preferably, the intake is 5X 107～5×1010The form of the seed comprises, more preferably takes up 1X 108～5×1010The form of the seed is contained, more preferably, the intake is 5X 108～5×1010The form of the seed comprises, more preferably takes up 5X 108～2×1010The mode of (a) contains lactic acid bacteria as an active ingredient.
In addition, for example, 10 is contained in 1g of lactobacillus culture7In the case of more than one lactic acid bacterium, the lactic acid bacterium culture as an active ingredient is preferably contained so as to be ingested in a single dose package in an amount of 5 to 1000g, more preferably 10 to 1000g, still more preferably 50 to 500g, still more preferably 70 to 300g, still more preferably 70 to 250g, and particularly preferably 80 to 200 g.
When the agent for improving the upper gastrointestinal flora according to the embodiment of the present invention is packaged in a single-dose package, a known package can be used. For example, paper, plastic, glass, nylon, stainless steel, aluminum, iron, copper, silver, bamboo, etc., are not particularly limited. However, in view of the fact that lactic acid bacteria are facultative anaerobes, it is preferable that lactic acid bacteria are not in contact with air or oxygen. For example, in the production process or packaging process of the agent for improving upper gastrointestinal flora according to the embodiment of the present invention, it is preferable to provide a process for eliminating the possibility of contact with oxygen, and to select a packaging material that does not allow oxygen to permeate into the package during storage after packaging.
In the embodiment of the present invention, the method for taking the agent for improving the upper gastrointestinal flora is not particularly limited, and any known taking method such as oral administration, tube administration, intestinal administration, vascular injection, liniment, suppository, etc. can be used, and in particular, oral taking can be suitably used.
In the embodiment of the present invention, the temperature of the agent for improving upper gastrointestinal flora at the time of ingestion is preferably-30 to 50 ℃, more preferably-20 to 45 ℃, still more preferably 0 to 30 ℃, still more preferably 0 to 20 ℃, and particularly preferably 0 to 10 ℃.
In the embodiment of the present invention, the upper gastrointestinal flora improving agent may contain other ingestible components, various additives, raw materials for foods, drinks, and medicines, and the like as components other than lactic acid bacteria.
Further, the agent for improving the upper gastrointestinal flora according to the embodiment of the present invention is preferably provided in the form of a functional food such as a food, a drink, a health food, a health functional food, and a supplement. Here, the functional food refers to a food having a body condition regulating function as a third function among food functions. Further, the health supplementary food means a health food identified by the Japan health & seed & Nutrition food Association (JHFA) of the finance and mass jurisdictions, and the health functional food means a specific health food and a nutritional functional food regulated by the Japan consumer transaction Association. In addition, the food and drink includes food and drink that does not conform to functional food. In addition, the agent for improving upper gastrointestinal flora according to the embodiment of the present invention may be formulated into a beverage, yogurt, cheese, dessert, etc. and processed to have a flavor and/or physical properties suitable for the form thereof so that the agent can be continuously ingested without feeling unpleasant.
Examples
Hereinafter, a test performed to confirm the effects of the embodiment of the present invention will be described in detail, but the present invention is not limited to the following configuration.
(example 1)
Comprises Lactobacillus gasseri: (Lactobacillus gasseri) A solid-state agent for improving the upper gastrointestinal flora, containing OLL2716 (FERM BP-6999) as an active ingredient, was prepared by the following method. Mixing raw milk, skimmed milk powder and water to make milk fat content reach 3.0 wt% and non-fat milk solid content reach 9.2 wt%, homogenizing the obtained mixture by conventional method, sterilizing, and cooling. Thereafter, Lactobacillus bulgaricus, Streptococcus thermophilus and Lactobacillus gasseri (Lactobacillus gasseri. (R.thermophilus) isolated from Mingzhi "Mingzhi ProBIO Yogurt LG 21" of K.K.)Lactobacillus gasseri) OLL2716 (FERM BP-6999), cultured according to a conventional method, and the resulting culture was used as example 1 (upper gastrointestinal flora improving agent). For convenience, the agent for improving the upper gastrointestinal flora is in the form of lactic acid bacteria containing an active ingredient which is taken directly.
The number of Lactobacillus gasseri OLL2716 (FERM BP-6999) lactic acid bacteria per 1g is about 107And (4) respectively.
(test method 1)
An intervention test was carried out using the agent for improving upper gastrointestinal flora of example 1 (hereinafter, this agent may be referred to as a test sample).
Specifically, 24 patients with helicobacter pylori-negative functional digestive tract disorder without organic disease were treated. In addition, as a control, 21 healthy persons without organic diseases and negative to helicobacter pylori were used.
Then, the above 24 patients with functional gastrointestinal disorders were allowed to continuously take the agent for improving the intestinal flora for 12 weeks at a dose of 118g for 1 day.
Further, gastric juices of the 24 patients with functional gastrointestinal disorders were obtained directly from the stomach through a naso-gastric tube (naso-gastric tube) in a state of overnight before and after the intake of the upper gastrointestinal flora improving agent and the continuous intake for 12 weeks. Similarly, gastric juice was obtained directly from the stomach of the 21 healthy persons over night through a naso-gastric tube (naso-gastric tube).
(specific of the gastric flora)
Bacterial DNA was extracted from the resulting gastric juice according to the conventional method in the Ultra Clean Soil DNA isolation kit (Mo Bio Laboratories, Carlsbad, CA). The extracted bacterial DNA was amplified by PCR, and the proportions of Bifidobacterium, Lactobacillus, Prevotella, Clostridium IV cluster, Clostridium XIVa subcluster, Clostridium IX cluster, Clostridium XI cluster, Clostridium XVIII cluster, and other bacteria were specified.
(Bifidobacterium in gastric juice)
In the above method, the ratio of bifidobacteria in the specific gastric juice is 0.0% (n =21) in the healthy human, whereas the ratio is 2.5% (n =24) before the intake of the agent for improving the upper gastrointestinal flora and is 0.4% (n =24) after the intake of the agent for improving the upper gastrointestinal flora in the patient with functional gastrointestinal disorder.
When the significance of the difference between "the ratio of bifidobacteria in gastric juice (n =21) in healthy humans" and "the ratio of bifidobacteria before ingestion of the agent for improving the flora in the upper gastrointestinal tract (n = 24)" in the above-mentioned patients was examined, the P value was less than 0.001, and it was judged that there was a significant difference.
When the significance of the difference between "the ratio of bifidobacteria in gastric juice (n =21) in healthy humans" and "the ratio of bifidobacteria after ingestion of the agent for improving the flora in the upper gastrointestinal tract (n = 24)" in the above-mentioned patients was examined, the P value was 0.003, and it was judged that there was a significant difference.
From the above, it can be seen that: bifidobacteria, which are not present in healthy people, are present in gastric juices of patients with functional digestive tract disorders. In addition, it is also known that: by continuously taking yogurt containing Lactobacillus gasseri OLL2716 (FERM BP-6999) lactic acid bacterium for 12 weeks, namely example 1, from a patient with functional digestive tract disorders, bifidobacteria in the stomach can be reduced, and a state close to that of a healthy person can be achieved.
(Probiotia in gastric juice)
In the method, the ratio of prevotella in the specific gastric juice is 37.4% (n =21) in the healthy human described above, whereas 28.3% (n =24) before the intake of the gastric flora improving agent and 39.8% (n =24) after the intake of the upper gastrointestinal flora improving agent are observed in the patient with functional gastrointestinal disorders described above.
When the significance of the difference was examined between "ratio of prevotella in gastric juice (n =21) in healthy persons" and "ratio of prevotella before ingestion of the improver of the flora in upper gastrointestinal tract (n = 24)" in the above-mentioned patients, the P value was 0.004, and it was judged that there was a significant difference.
When the significance of the difference was examined between "the ratio of prevotella in gastric juice (n =21) in healthy persons" and "the ratio of prevotella after ingestion of the agent for improving the flora in the upper gastrointestinal tract (n = 24)" in the patients, the P value was 0.001, and it was judged that there was a significant difference.
From the above, it can be seen that: the proportion of prevotella in gastric juice of patients with functional digestive tract disorders is low compared to healthy persons. Further, by continuously taking yogurt containing Lactobacillus gasseri OLL2716 (FERM BP-6999) lactic acid bacterium for 12 weeks, namely, example 1, from a patient with functional digestive tract disorders, the amount of prevotella in the stomach can be increased, and the condition close to that of a healthy person can be achieved.
While several embodiments and/or examples of the present invention have been described in detail, it will be readily apparent to those skilled in the art that many modifications may be made to the embodiments and/or examples without materially departing from the novel teachings and advantages of this invention. Accordingly, many of the modifications described above are intended to be included within the scope of the present invention.
The contents of the documents described in the present specification and the contents of the japanese application specification that is the basis of the priority of the paris convention of the present application are incorporated herein by reference.
Claims (6)
1. The application of lactobacillus in preparing the flora improving agent in the upper digestive tract is characterized in that: the above-mentioned agent for improving upper gastrointestinal flora is used for positive and negative helicobacter pylori, and the above-mentioned improvement of upper gastrointestinal flora means a decrease in upper gastrointestinal bifidobacteria and/or an increase in upper gastrointestinal prevotella,
the lactobacillus is Lactobacillus gasseri (L.) (Lactobacillus gasseri) OLL 2716 (FERM BP-6999)。
2. The use of claim 1, wherein: the above-mentioned improvement of the flora in the upper gastrointestinal tract means a decrease of bifidobacteria in the stomach and/or an increase of prevotella in the stomach.
3. The use of claim 1, wherein: the above agent for improving upper digestive tract flora is used for helicobacter pylori-negative patients.
4. The use of claim 1, wherein: the daily dose of the above-mentioned lactic acid bacteria to human is 2X 107～5×1010And (4) respectively.
5. The use of claim 1, wherein: contains 10 per 1g of the above lactobacillus culture7In the case of more than one lactic acid bacterium, the daily dose of the lactic acid bacterium culture to a human is 5 to 1000 g.
6. The use of claim 1, wherein: the agent for improving upper gastrointestinal flora exerts an effect of improving upper gastrointestinal flora within 4 weeks after ingestion.
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| JP2016-122155 | 2016-06-20 | ||
| JP2016122155 | 2016-06-20 | ||
| PCT/JP2017/022065 WO2017221799A1 (en) | 2016-06-20 | 2017-06-15 | Upper gastrointestinal flora-improving agent |
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| CN109310718A CN109310718A (en) | 2019-02-05 |
| CN109310718B true CN109310718B (en) | 2022-06-17 |
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| US (1) | US20190151381A1 (en) |
| JP (1) | JP7101354B2 (en) |
| CN (1) | CN109310718B (en) |
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| WO (1) | WO2017221799A1 (en) |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6596530B1 (en) * | 1999-06-24 | 2003-07-22 | Meiji Dairies Corporation | Strain of Lactobacillus gasseri |
| WO2015129281A1 (en) * | 2014-02-28 | 2015-09-03 | 株式会社明治 | Prophylactic and/or therapeutic agent for functional gastrointestinal disorders |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101522887B (en) * | 2007-02-13 | 2012-07-11 | 森永乳业株式会社 | Novel lactic acid bacteria |
| JP5300772B2 (en) * | 2010-03-26 | 2013-09-25 | 森永乳業株式会社 | Novel lactic acid bacteria and pharmaceuticals, foods and drinks, and feeds containing the novel lactic acid bacteria |
| MX354047B (en) * | 2011-06-08 | 2018-02-09 | Novozymes As | SPRAY-DRIED <i>LACTOBACILLUS</i> STEMS / CELLS AND THE USE OF SAME AGAINST <i>HELICOBACTER PYLORI. |
| CN104797265A (en) * | 2012-11-16 | 2015-07-22 | 可尔必思株式会社 | Stress-induced bowel disorder-relieving agent comprising specific lactobacillus gasseri strain or treatment product thereof |
-
2017
- 2017-06-15 SG SG11201810492QA patent/SG11201810492QA/en unknown
- 2017-06-15 CN CN201780038418.3A patent/CN109310718B/en active Active
- 2017-06-15 WO PCT/JP2017/022065 patent/WO2017221799A1/en active Application Filing
- 2017-06-15 JP JP2018523986A patent/JP7101354B2/en active Active
- 2017-06-15 US US16/308,526 patent/US20190151381A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6596530B1 (en) * | 1999-06-24 | 2003-07-22 | Meiji Dairies Corporation | Strain of Lactobacillus gasseri |
| WO2015129281A1 (en) * | 2014-02-28 | 2015-09-03 | 株式会社明治 | Prophylactic and/or therapeutic agent for functional gastrointestinal disorders |
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| JPWO2017221799A1 (en) | 2019-04-11 |
| CN109310718A (en) | 2019-02-05 |
| WO2017221799A1 (en) | 2017-12-28 |
| JP7101354B2 (en) | 2022-07-15 |
| US20190151381A1 (en) | 2019-05-23 |
| SG11201810492QA (en) | 2019-01-30 |
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